Association of beta-arrestin and TRAF6 negatively regulates Toll-like receptor-interleukin 1 receptor signaling

Wang Y, Tang Y, Teng L, Wu Y, Zhao X and Pei G
Source: Nat Immunol
Publication Date: (2006)
Issue: 7(2): 139-47
Research Area:
Cancer Research/Cell Biology
Immunotherapy / Hematology
Cells used in publication:
Species: human
Tissue Origin: blood
Nucleofector® I/II/2b
Tumor necrosis factor receptor-associated factor 6 (TRAF6) is critical for mediating Toll-like receptor (TLR)-interleukin 1 receptor (IL-1R) signaling and subsequent activation of NF-kappaB and AP-1, transcriptional activators of innate immunity. Here we show that beta-arrestins, a family of multifunctional proteins, directly interacted with TRAF6 after TLR-IL-1R activation. Formation of the beta-arrestin-TRAF6 complex prevented autoubiquitination of TRAF6 and activation of NF-kappaB and AP-1. Endotoxin-treated beta-arrestin 2-deficient mice had higher expression of proinflammatory cytokines and were more susceptible to endotoxic shock. Thus, beta-arrestins are essential negative regulators of innate immune activation via TLR-IL-1R signaling.